U.S. Pat. No. 6,165,500 to Cevc describes a “preparation for the application of agents . . . provided with membrane-like structures consisting of one or several layers of amphiphilic molecules, or an amphiphilic carrier substance, in particular for transporting the agent into and through natural barriers such as skin and similar materials.” Abstract. These transfersomes “consist of one or several components[, m]ost commonly a mixture of basic substances, one or several edge-active substances, and agents [ ].” Col. 5, lines 28-30. According to U.S. Pat. No. 6,165,500, “[l]ipids and other amphiphiles are best suited basic substances; surfactants or suitable solvents are the best choice from the point of view of edge-active substances[, and a]ll of these can be mixed with agents in certain proportions depending both on the choice of the starting substances and on their absolute concentration.” Col. 5, lines 30-35.
U.S. Patent Application Publication No. US 2004/0071767 to Cevc et al. describes “formulations of nonsteroidal anti-inflammatory drugs (NSAIDs) based on complex aggregates with at least three amphiphatic components suspended in a . . . pharmaceutically acceptable . . . medium.” Abstract. “One of these components is capable of forming stable, large bilayer membranes on its own. The other at least two amphiphatic components, including an NSAID, tend to destabilise such membranes.” Paragraph [0002].
U.S. Patent Application Publication No. US 2004/0105881 to Cevc et al. describes extended surface aggregates, “suspendable in a suitable liquid medium and comprising at least three amphiphats (amphiphatic components) and being capable to improve the transport of actives through semi-permeable barriers, such as the skin, especially for the non-invasive drug application in vivo by means of barrier penetration by such aggregates.” Paragraph [0002]. “The three amphiphats include at least one membrane forming compound (MFC), which can form the membrane of [the aggregates], and at least two membrane destabilising compounds (MDC1 and MDC2) differentiated by their capability of forming smaller aggregates (with no extended surfaces) by either themselves or else in combination with each other and/or characterized by their relatively high solubility in [the] suitable liquid medium. Paragraph [0002]. US 2004/0105881 specifically discloses that “incorporation of a surfactant into a bilayer membrane that is built from another less soluble amphiphat, such as a phospholipid, can increase the flexibility of the resulting complex membrane . . . promot[ing] the capability of complex aggregates . . . to cross pores in a semi-permeable membrane that otherwise would prevent comparably large aggregates from crossing.” Paragraph [0015]. Citation of any reference in this section of the application is not an admission that the reference is prior art to the application. The above noted publications are hereby incorporated by reference in their entirety.